Atherosclerosis and thrombosis are frequent causes of arterial obstruction.
Atherosclerosis is responsible for most cases of arterial occlusion affecting the myocardium, brain and peripheral arteries.
Arterial obstruction or narrowing causes a reduction in blood flow either during exercise or at rest. The clinical signs result from ischaemia. The atherosclerotic lesions which affect large and small blood vessels in diabetics are very similar to those which appear in non-diabetics; however, they appear earlier, worsen more quickly and are more frequent in the case of diabetics.
Distal arterial occlusion below the knee together with microvascular alterations and neurological lesions are responsible for gangrene. The symptoms are intermittent claudication and pain at rest caused by ischaemia. Diabetic foot, which is caused by a combination of vasculopathy, neuropathy and infection, is one of the most dangerous complications of diabetes, and is the cause of most amputations. Amputation of the foot or leg is five times as frequent in diabetics as in non-diabetics. Angina and myocardial infarction are the most frequent complications of occlusion or stenosis of the coronary artery.
These local actions, together with those of the autonomic nervous system and the vascular system, cause vasoconstriction when activated, such as after exposure to cold; conversely, a reduction in these effects results in vasodilatation.
The development of collateral circulation which results from stenosis or a major obstruction of the arteries influences the degree of ischaemia. Some collateral vessels are present in normal tissue, but do not dilate until arterial obstruction appears, while other capillaries develop in weeks or months. The adrenergic nerves, which are part of the autonomic nervous system, are responsible for vasoconstriction or dilatation of the collateral vessels in response to the increase in arterial pressure, with the result that the flow of blood to the tissue is improved.
Substances produced by the endothelial cells which induce new blood vessel formation (neoangiogenesis) and vasodilatation were recently discovered. The production of VEGF (Vascular Endothelial Growth Factor), which seems to be responsible for the majority of the angiogenic and` vasodilatory effect that results from stenosis or arterial obstruction, appears to be particularly important.
Experiments with isolated animal muscles have demonstrated that continuous electrical stimulation for 5 days (stimulation of 0.3 ms of amplitude, frequency of 150 Hz and voltage of 0.1 V) increases VEGF production, the number of capillaries and the blood flow (Kanno S, Odam Abe M. Circulation 1999; 99, 2682-87).
Although the experiments described above seem to suggest that electrical stimulation of the muscles has beneficial effects on the circulation, the problem remains of how to induce a prolonged stimulation on nerves and muscles in humans.
Patients suffering from acute ischaemia or initial infarction present increased production of VEGF in the myocardium and in the endothelial cells of the capillaries and arterioles (Lee S H, Wolf P L, Escudero R, N. Engi. J. Med. 2000; 342, 626-33).
The revascularisation induced by a transmyocardial laser with the aim of reducing angina pain is accompanied by an increase in VEGF and angiogenesis (Horvath, Chiu E, Maun A C, Annals of Thoracic Surgery 1999; 68, 825-29).
Modern technology offers some highly sophisticated instruments which allow the use of new techniques such as transmyocardial laser revascularisation, but the results are still limited. An electrical phoryngeal neuromuscolar stimulator is disclosed in WO 99/24111.
The treatment of peripheral vascular disease is usually unsatisfactory. Vasodilators have a modest effect, and sympathectomy is ineffective. The injection of VEGF produced by GMO (Genetically Modified Organisms) is not without side effects. The only therapeutic solution is vascular surgery.
In practice, no really effective system for the treatment of peripheral vascular disorders has yet been found. Vasodilators give poor results, treatment with VEGF based on recombinant DNA is not safe enough, and even surgery is just one of the various alternatives, which has not demonstrated any real efficacy.